The role of alpha7 and alpha4beta2 nicotinic receptors in the nicotine-induced anxiolytic effect in zebrafish.

The role of alpha7 and alpha4beta2 nicotinic receptors in the nicotine-induced anxiolytic effect in zebrafish.
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α7和α4Beta2烟碱受体在斑点诱导的斑马鱼中的作用。

DOI:
10.1016/j.physbeh.2008.07.009
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发表时间:
2008-10-20
影响因子:
2.9
通讯作者:
Levin, Edward D.
Levin, Edward D.
中科院分区:
医学3区
文献类型:
--
作者:
Bencan, Zachary;Levin, Edward D.

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斑马鱼(Danio rerio)是研究发育包括神经发育的分子机制的重要工具。最近,它们开始被用于研究神经药理学和神经毒理学。这条研究路线的关键是研究斑马鱼行为功能的方法。以前的研究比较了斑马鱼与哺乳动物模型,以确定运动行为,学习和记忆的相似性和差异。关于斑马鱼的应激反应、焦虑行为以及药理学反应的研究相对较少。我们已经开发了一种测试斑马鱼来评估压力反应和焦虑:新颖的坦克潜水测试。在这个短暂的测试中,通常斑马鱼潜入到新水箱的底部,然后在5分钟的测试中逐渐开始探索水箱的更高水平。尼古丁在啮齿动物和人类中具有抗焦虑作用,被发现可以减少斑马鱼这种新颖的坦克潜水反应。本研究检测了尼古丁作用中尼古丁受体亚型的选择性。使用两种烟碱受体亚型选择性拮抗剂:MLA(α7拮抗剂)和DHβE(α4β2拮抗剂)。我们重复了我们以前发现的尼古丁的抗焦虑作用,尼古丁治疗后鱼的底部停留显着减少。这种尼古丁诱导的抗焦虑作用被MLA和DHβE逆转,表明尼古丁α7和α4β2受体都参与了尼古丁对焦虑的作用。
Zebrafish (Danio rerio) have been widely used to study the molecular mechanisms of development including neurodevelopment. More recently, they have begun to be used to study neuropharmacology and neurotoxicology. Critical for this line of research are methods to study behavioral function in zebrafish. Previous studies have compared zebrafish with mammalian models to determine similarities and differences in locomotor behavior, learning and memory. Relatively little research has been conducted on stress response and anxiety behavior as well as the pharmacologic response in zebrafish. We have developed a test for zebrafish to assess stress response and anxiety: the novel tank diving test. In this short test normally zebrafish dive to the bottom of a novel tank and then gradually over the 5-min test begin exploring higher levels of the tank. Nicotine, which has anxiolytic effects in rodents and humans was found to diminish this novel tank diving response in zebrafish. The current study examined the nicotinic receptor subtype selectivity involved in the actions of nicotine. Two the nicotinic receptor subtype selective antagonists were used: MLA (an α7 antagonist) and DHβE (an α4β2 antagonist). We replicated our previous finding of the anxiolytic effect of nicotine with significantly less bottom dwelling by the fish after nicotine treatment. This nicotine-induced anxiolytic effect was reversed by both MLA and DHβE, indicating that both nicotinic α7 and α4β2 receptors are involved in the nicotinic effect on anxiety.
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